Thesis supervisor: Balázs Hangya
Location of studies (in Hungarian): KOKI Abbreviation of location of studies: SE
Description of the research topic:
Diseases associated with dementia affect more than 27 million people worldwide and cost over $ 600 million a year (Wimo and Prince, 2010; Wittchen et al., 2011). Neuromodulatory systems have a long-established pathophysiological role in these diseases, examples include the degeneration of cholinergic neurons in Alzheimer's disease, and the gradual loss of dopaminergic neurons in Parkinson's disease.
Neuromodulatory systems play an important role in learning and other cognitive functions, but it is not known how they interact to exert their joint control over these functions. By understanding the relationships between cholinergic, dopaminergic, and other neuromodulatory cell activity and how they affect learning processes, we have a chance to better understand neurodegenerative dementias, which may even lead to better therapeutic procedures in the future.
In our studies, our main foci are basal forebrain cholinergic neurons (Everitt and Robbins, 1997) and midbrain dopaminergic neurons (Cohen et al., 2012). In addition, other inhibitory GABAergic and excitatory glutamatergic cells of the neuromodulatory centers as well as other neuromodulatory systems such as cholinergic cells of the lateral septum, noradrenergic and serotonergic systems are also examined.
We also test the clinical relevance of the information obtained from the above experiments. For this purpose, we use experimental rodent disease models and conduct human psychophysical and EEG experiments.
A variety of techniques are used to perform rodent experiments: well-controlled mouse behavioral tests, multichannel electrophysiological measurements, optogenetic cell type identification, optogenetic manipulations, and novel fiber photometry techniques.
Aims
1. Simultaneous study of neuromodulatory systems during learning
We are currently investigating the cholinergic and dopaminergic systems simultaneously to explore the inter-relationships between the two neuromodulatory systems. The study is extended to the noradrenergic and serotonergic systems, as well as mouse models of aging, Alzheimer's disease, and Parkinson's disease. The results are also compared with data from human patients.
2. Examination of the lateral septum
The area of the lateral septum is important for the regulation of social behavior and anxiety. However, the exact role of the lateral septal cell types in these processes is not yet known. We examine anatomically and genetically defined neuron types in the context of different behaviors. The lateral septal area is vulnerable to Alzheimer’s disease, the relevance of which is also being explored.
3. Restoration of learning impairments by deep brain stimulation of the basal forebrain
We test whether deep brain stimulation could improve cognitive function of mice in mouse models of neurodegenerative dementias and in the context of age-related cognitive decline.
These experiments help explore the role of neuromodulatory systems in normal learning and may bring us closer to understanding neurodegenerative dementias.
Hivatkozások
Cohen, J.Y., Haesler, S., Vong, L., Lowell, B.B., and Uchida, N. (2012). Neuron-type-specific signals for reward and punishment in the ventral tegmental area. Nature 482, 85–88.
Everitt, B.J., and Robbins, T.W. (1997). Central cholinergic systems and cognition. Annu. Rev. Psychol. 48, 649–684.
Wimo, A., and Prince, M. (2010). World Alzheimer Report 2010. The Global Economic Impact of Dementia. Alzheimer’s Dis. Int.
Wittchen, H.U., Jacobi, F., Rehm, J., Gustavsson, A., Svensson, M., Jönsson, B., Olesen, J., Allgulander, C., Alonso, J., Faravelli, C., et al. (2011). The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21, 655–679.
Deadline for application: 2022-05-01
2024. IV. 17. ODT ülés Az ODT következő ülésére 2024. június 14-én, pénteken 10.00 órakor kerül sor a Semmelweis Egyetem Szenátusi termében (Bp. Üllői út 26. I. emelet).
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